The morbidity and mortality of acute myelogenous leukemia in man are primarily a result of leukopenia, thrombocytopenia, and anemia. These cytopenias result from decreased hematopoiesis. The mechanism by which acute leukemia inhibits normal hematopoiesis is unknown. We propose to use the granulocytic leukemia of RF/UN mice as a model system to study the pathophysiology of acute myelogenous leukemia in man. Both in vitro and in vivo assays of hematopoietic stem cells will be employed to determine if leukemic cells directly (by cell-cell contact) or indirectly (humoral effect) inhibit normal hematopoiesis. Simultaneously with the pathophysiologic studies, we will evaluate the usefulness of this animal leukemia as a chemotherapeutic model of acute myelogenous leukemia in man. This will be accomplished by comparing the drug responsiveness of this disease to that of other animal leukemias and to leukemia in man.